In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3-4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant leads to reduced cell surface expression of ICAM-2. These data provide a resource for comparative genomic studies of HIV and/or SIV pathogenesis and may help to elucidate the mechanisms by which SIV-infected sooty mangabeys avoid AIDS.
Acquired Immunodeficiency Syndrome, Amino Acid Sequence, Animals, Cell Adhesion Molecules, Cercocebus atys, Exons, Female, Frameshift Mutation, Genetic Predisposition to Disease, Genetic Variation, Genome, Genomics, HIV, Host Specificity, Humans, Macaca, Sequence Deletion, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, Species Specificity, Toll-Like Receptor 4, Transcriptome, Whole Genome Sequencing
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Open access content For open access content published under a Creative Commons license, the published version can be deposited immediately on publication, alongside a link to the URL of the published article on the journal's website. In all cases, the requirement to link to the journal's website is designed to protect the integrity and authenticity of the scientific record, with the online published version on nature.com clearly identified as the definitive version of record.
Palesch, David; Bosinger, Steven E.; Tharp, Gregory K.; Vanderford, Thomas H.; Paiardini, Mirko; Chahroudi, Ann; Johnson, Zachary P.; Kirchhoff, Frank; Hahn, Beatrice H.; Norgren, Robert B.; Patel, Nirav B.; Sodora, Donald L.; Dawoud, Reem A.; Stewart, Caro-Beth; Seepo, Sara M.; Harris, R. Alan; Liu, Yue; Raveendran, Muthuswamy; Han, Yi; English, Adam; Thomas, Gregg W.C.; Hahn, Matthew W.; Pipes, Lenore; Mason, Christopher E.; Muzny, Donna M.; Gibbs, Richard A.; Sauter, Daniel; Worley, Kim; Rogers, Jeffrey; and Silvestri, Guido, "Sooty Mangabey Genome Sequence Provides Insight into AIDS Resistance in a Natural SIV Host" (2018). Journal Articles: Genetics, Cell Biology & Anatomy. 35.